TY - JOUR

T1 - Lifestyle in Pregnancy and Hypospadias in Sons

T2 - A Study of 85,923 Mother-Son Pairs from Two Danish Pregnancy Cohorts

AU - Kjersgaard, Camilla Lomholt

AU - Arendt, Linn Håkonsen

AU - Ernst, Andreas

AU - Lindhard, Morten Sondergaard

AU - Olsen, Jørn

AU - Henriksen, Tine Brink

AU - Strandberg-Larsen, Katrine

AU - Ramlau-Hansen, Cecilia Host

PY - 2022

Y1 - 2022

N2 - Purpose: Hypospadias is one of the most frequent male congenital malformations. It remains controversial whether maternal lifestyle during pregnancy may affects the risk of having a son with hypospadias, especially for smoking with many suggesting lower risk. We assessed the individual and joint associations between maternal cigarette smoking, prepregnancy body mass index (BMI), alcohol consumption, binge drinking, and caffeine consumption and occurrence of hypospadias in sons. Patients and Methods: This cohort study utilized the Danish National Birth Cohort and the Aarhus Birth Cohort, holding detailed information on lifestyle factors in early pregnancy between 1989 and 2012. The Danish health registers were used to identify boys with hypospadias, according to International Classification of Diseases. Potential confounders and covariates were identified by literature search and use of directed acyclic graphs. Missing data were handled by multiple imputation and Cox proportional hazards models were applied to analyse data. Results: In total, 85,923 live-born singleton boys were included in the study of whom 502 (0.6%) were diagnosed with hypospadias. Maternal smoking in early pregnancy was associated with lower occurrence of hypospadias. An increase of one cigarette smoked per day was associated with lower risk of having a son with hypospadias (adjusted hazard ratio (HR) 0.97 (95% confidence interval (CI) 0.94, 1.00)). However, sub-analyses suggested that the results may be prone to unadjusted confounding. We found no association between prepregnancy BMI, alcohol consumption, binge drinking, or caffeine consumption and hypospadias. Conclusion: Maternal smoking during pregnancy was associated with lower occurrence of hypospadias but we cannot exclude uncontrolled confounding. The other investigated maternal lifestyle factors were not associated with hypospadias in sons.

AB - Purpose: Hypospadias is one of the most frequent male congenital malformations. It remains controversial whether maternal lifestyle during pregnancy may affects the risk of having a son with hypospadias, especially for smoking with many suggesting lower risk. We assessed the individual and joint associations between maternal cigarette smoking, prepregnancy body mass index (BMI), alcohol consumption, binge drinking, and caffeine consumption and occurrence of hypospadias in sons. Patients and Methods: This cohort study utilized the Danish National Birth Cohort and the Aarhus Birth Cohort, holding detailed information on lifestyle factors in early pregnancy between 1989 and 2012. The Danish health registers were used to identify boys with hypospadias, according to International Classification of Diseases. Potential confounders and covariates were identified by literature search and use of directed acyclic graphs. Missing data were handled by multiple imputation and Cox proportional hazards models were applied to analyse data. Results: In total, 85,923 live-born singleton boys were included in the study of whom 502 (0.6%) were diagnosed with hypospadias. Maternal smoking in early pregnancy was associated with lower occurrence of hypospadias. An increase of one cigarette smoked per day was associated with lower risk of having a son with hypospadias (adjusted hazard ratio (HR) 0.97 (95% confidence interval (CI) 0.94, 1.00)). However, sub-analyses suggested that the results may be prone to unadjusted confounding. We found no association between prepregnancy BMI, alcohol consumption, binge drinking, or caffeine consumption and hypospadias. Conclusion: Maternal smoking during pregnancy was associated with lower occurrence of hypospadias but we cannot exclude uncontrolled confounding. The other investigated maternal lifestyle factors were not associated with hypospadias in sons.

KW - smoking

KW - prenatal exposures

KW - alcohol

KW - caffeine

KW - BMI

KW - birth defects

KW - ENVIRONMENTAL RISK-FACTORS

KW - MATERNAL SMOKING

KW - BIRTH-WEIGHT

KW - CRYPTORCHIDISM

KW - POPULATION

KW - BOYS

KW - PREVALENCE

KW - EXPOSURES

KW - ETIOLOGY

U2 - 10.2147/CLEP.S335877

DO - 10.2147/CLEP.S335877

M3 - Journal article

C2 - 35173488

VL - 14

SP - 149

EP - 157

JO - Clinical Epidemiology

JF - Clinical Epidemiology

SN - 1179-1349

ER -